Magnesium trisilicate suitable for preparation of medicament adsorbates of antinauseants

ABSTRACT

A medicament adsorbate containing a magnesium trisilicate having a surface area of at least 400 m2/g and having a flake-like structure with multiple interstitial spaces, and having adsorbed therein from about 1% to about 20% by weight of the adsorbate of a medicament drug, wherein the medicament drug is an antinauseant.

This is a continuation in part of copending U.S. application Ser. No.516,002 filed July 20, 1983, now U.S. Pat. No. 4,581,232.

This invention relates to a medicament adsorbate composition containingmagnesium trisilicate and in particular to a medicament adsorbate whichemploys a magnesium trisilicate having a surface area of at least 400 m²/g with a surface structure having multiple interstitial-flaked spaces.

The use of magnesium trisilicates in the preparation of medicamentadsorbates has been taught in the literature as a method to renderbitter drug principles tasteless in liquid, tablet and chewable dosageforms which become readily bioavailable when the adsorbate reaches thelow pH acid media of the stomach.

U.S. Pat. No. 3,085,942 to Magid discloses the formation of anantitussive composition using dextromethorphan and its acid additionsalts adsorbed, in part, on magnesium trisilicate. Magid notes thatparticle size of the magnesium trisilicate is not critical in preparingthe adsorbates and that average particle sizes of about 0.1 to about 150microns are usable. Magid also notes that when the ingredients areintimately mixed, the bitter taste associated with dextromethorphan isreduced or eliminated. The adsorbate may be mixed with other ingredientsto form compressed tablets, candy lozenges, chewing gum tablets and thelike.

Most of these products when placed in the mouth and chewed, however,cause release of the medicament drug from the adsorbate resulting in thesensation of off-taste medicine to the user. Efforts therefore have beendiverted to the development of products that either reduce the amount ofmedicament or mask the after-taste, such as by minimizing stimulation ofthe taste buds. These methods have involved various techniques such asmicroencapsulation as a method of coating particles or liquid dropletswith edible polymeric materials; adsorption onto substrates capable ofkeeping the drugs adsorbed while in the mouth but releasing themeventually in the stomach or gastrointestional tract; spray congealingand spray coating involving taste masking of materials with fatty acidsor monoglycerides and diglycerides of edible fatty acids; formation ofdifferent salts or derivatives by modification of the chemicalcomposition of the drug substance itself.

It would, therefore, be desirable to develop a medicament adsorbate thatwould enable such products to be made without the bitter after-tastecharacteristics, that result from incorporating effective amounts ofbitter medicaments, and that can be made and used easily withoutelaborate processing procedures.

Applicants have unexpectedly discovered that use of a particularmagnesium trisilicate, rather than conventional magnesium trisilicatesbroadly, such as described by Magid, results in the formation of anadsorbate having adsorbency potentials greater than commerciallyavailable grades of magnesium silicates and achieves optimum medicamenttaste-masking characteristics while providing rapid bioavailability.

In particular, applicants have found that an adsorbate exhibitingunexpected results is only achieved with a magnesium trisilicate havinga critical surface area of at least 400 m² /g when the particles of themagnesium trisilicate exhibit a flake-like structure having multipleinterstitial spaces.

This particular magnesium trisilicate has been found to be suitable forpreparation of tasteless medicament adsorbates.

While the invention is not to be limited to theoretical considerations,it is believed that the surface area of the magnesium trisilicatecoupled with the flaked-like surface results in an unusual ability toadsorb the medicament drug within the channels, convolutions orinterstitial spaces of the adsorbate. Once adsorbed within the magnesiumtrisilicate, the drug is not available for organoleptic taste prior topassage into the digestive tract and subsequent desorption by thegastric juice. This pronounced adsorption effect is not found in normalcommercially available magnesium trisilicate and appears to be unrelatedto particle size.

Accordingly, the applicants have unexpectedly discovered a medicamentadsorbate which comprises magnesium trisilicate having a surface area ofat least 400 m² /g which has a flake-like structure having multipleinterstitial space, containing from about 1% to about 20% by weight ofthe adsorbate of a medicament drug.

Applicants have also unexpectedly discovered a process for preparing themedicament adsorbate which process involves dissolving the medicamentdrug in a solvent, admixing magnesium trisilicate having a surface areaof at least 400 m² /g which has a flake-like structure with multipleinterstitial spaces therewith to prepare a mass having a homogenousconsistency to enable the medicament drug to migrate within themagnesium trisilicate interstitial spaces and recovering the medicamentadsorbate product.

The medicament adsorbate of the invention may further include apharmaceutically acceptable carrier and be in the form of a lozenge,tablet, toffee, nougat, chewy candy, and chewing gum.

Referring to the drawings:

FIG. 1 represents a photomicrograph of magnesium trisilicate of thisinvention magnified 5000×.

FIG. 2 represents a photomicrograph of a dextromethorphan HBr adsorbateof this invention magnified 5000×.

FIG. 3 represents a photomicrograph of a normal magnesium trisilicatemagnified 5000×.

FIG. 4 represents a photomicrograph of a normal dextromethorphan HBradsorbate magnified 5000×.

The magnesium trisilicate of the invention is a fine, white odorlesspowder free from grittiness having a surface area of at least 400 m² /g,and preferably at least 400 m² /g to about 1000 m² /g and mostpreferably from about 440 to about 600 m² /g which has a flake-likestructure with multiple interstitial spaces. It has been unexpectedlyfound that magnesium trisilicates having these characteristics when usedas an adsorbent aid in masking the bitter after-taste associated withvarious drug compounds.

The instant magnesium trisilicate is distinct from normally availablemagnesium trisilicates. The term magnesium trisilicate does not have aprecise description but approximates the formula 2MgO₃ SiO₂.xH₂ O. Thephysical texture and absorptive properties of magnesium silicates havebeen heretofore varied depending predominately upon their mode ofpreparation. These materials, however, generally possess a water contentof 17 to 34%, a minimum of 20% magnesium oxide, a minimum of 45% silicondioxide, and a ratio of MgO to SiO₂ of about 2.10 to about 2.30.

The normal magnesium trisilicate has a surface area of less than 400 m²/g and preferably less than 250m² /g. These materials likewise areglobular semi-spherical structures which are non-flake in appearance andare void of interstitial spaces. Such materials when used as anadsorbent have heretofore failed to effectively mask the bitter tasteassociated with adsorbed medication while maintaining satisfactorylevels of drug activity. It is believed that such conventional materialshave heretofore only been able to partially adsorb the medicament asdescribed in U.S. Pat. No. 3,085,942 to Magid on the surface of themagnesium trisilicate. Since the surface of these materials isrelatively smooth, efficient adsorption has not been possible andadditional after-taste masking ingredients have been employed.

The method of making the magnesium trisilicates used in this inventionis not critical and is not considered a part of this invention.Magnesium trisilicates of this invention are believed to occur naturallyor may be prepared by standard techniques well known to the ordinaryskilled artisan which would not involve undue experimentation. Suchtechniques generally use normal reactants, such as sodium silicate andmagnesium sulfate which are reacted under heat, the magnesiumtrisilicate is precipitated and recovered. See for example U.S. Pat. No.3,272,594.

The medicament drugs used herein may be selected from a wide variety ofdrugs and their acid addition salts. Both organic and inorganic saltsmay be used provided the drug maintains its medicament value and issoluble in the solvent. Exemplary acid salts include hydrochloride,hydrobromide, orthophosphate, benzoate, maleate, tartrate, succinate,citrate, salicylate, sulfate, and acetate.

The weight percent of the drug or its acid addition salt thereof, basedon the weight of the adsorbate is preferably from about 1% to about 20%,and most preferably about 5% to about 15%, which amounts will varydepending upon the therapeutic dosage permitted.

Suitable categories of drugs that may be employed in the instantabsorbate may vary widely and generally represent any stable adsorbatedrug combination. Illustrative categories and specific examples include:

(a) Antitussives, such as dextromethorphan, dextromethorphanhydrobromide, noscapine, carbetapentane citrate, and chlophedianolhydrochloride;

(b) Antihistamines, such as chlorpheniramine maleate, phenindaminetartrate, pyrilamine maleate, doxylamine succinate, phenyltoloxaminecitrate, diphenhydramine hydrochloride, promethazine and triprolidine;

(c) Decongestants, such as phenylephrine hydrochloride,phenylpropanolamine hydrochloride, pseudoephedrine hydrochloride,ephedrine;

(d) Various Alkaloids, such as codeine phosphate, codeine sulfate andmorphine: and

(e) Antinauseants, such as dimenhydrinate and meclizine.

These materials may be used alone or in combination on the adsorbatewithin the ranges specified above.

A particularly effective medicament adsorbate has been prepared usingdimenhydrinate.

The medicament adsorbate of the invention can be prepared byconventional granulation and or slurry techniques. Both processesinvolve the initial step of dissolving the medicament drug in a suitableinert solvent and then mixing with the magnesium trisilicate. Solventconcentrations may vary widely but are generally from about 15% to about60% by weight of the total composition. When mixing is performed withlow amounts of solvent, for example 15% to about 35% by weight of thetotal composition, the resulting granulated product is removed and driedto a predetermined moisture content between 5% and 20% by weight of thefinal composition. When higher solvent concentrations are employed aslurry is formed containing the drug and magnesium trisilicate. Solventconcentrations may range from about 30% to 60% by weight of the totalcomposition for optimum results. The solvent is then removed and theadsorbate recovered and used as a paste or dried to a free flowingpowder.

Any solvent may be used in the inventive process to prepare theadsorbate providing it is capable of dissolving the medicament drug.Representative solvents include water; polyhalogenated lowerhydrocarbons such as chloroform, methylene chloride; lower alcohols,such as methanol, ethanol, propanol and butanol; and aromatic solventssuch as benzene, with water being the preferred solvent.

The medicament adsorbate once prepared may be stored for future use orformulated with conventional additives, that is pharmaceuticallyacceptable carriers, to prepare medicated compositions which offer avariety of textures to suit particular applications. Such compositionsmay be in the form of a lozenge, tablet, toffee, nougat, chewy candy,chewing gum, and so forth. The pharmaceutically acceptable carriers maybe selected from a wide range of materials. Without being limitedthereto, such materials include diluents, binders and adhesives,lubricants, disintegrants, colorants, flavorings, sweeteners andmiscellaneous materials such as buffers and adsorbents in order toprepare a particular medicated composition. The preparation ofconfectionery and chewing gum products is historically well known andhas changed very little over the years.

Lozenges are flavored medicated dosage forms intended to be sucked andheld in the mouth. They may be in the form of various shapes, the mostcommon being flat, circular, octagonal and biconvex forms. The lozengebases are generally in two forms, hard, boiled candy lozenges andcompressed tablet lozenges.

The hard boiled candy lozenges are prepared from a mixture of sugar andother carbohydrates that are kept in an amorphous or glassy condition.This form can be considered a solid syrup of sugars generally havingfrom 0.5 to 1.5% moisture. Such materials normally contain up to 92%corn syrup, up to 55% sugar and from 0.1% to 5.0% water. The syrupcomponent generally is prepared from corn syrups high in fructose, butmay include other materials. Further ingredients such as flavorings,sweeteners, acidulents, colorants and so forth may also be added. Incontrast, compressed tablet lozenges contain particular materials andare formed into structures under pressure. They generally contain sugarsin amounts up to 95% and typical tablet excipients such as binders andlubricants as well as flavors, colorants and so forth.

The lozenges may be made of soft confectionary materials such as thosecontained in nougat. These materials contain two primary components,namely a high boiling syrup such as corn syrup or the like, and arelatively light textured frappe, generally prepared from gelatin, eggalbumen, milk proteins such as casein, and vegetable proteins such assoy protein, and the like. The frappe is generally relatively light, andmay, for example, range in density from about 0.5 to about 0.7g/cc.

By comparison, the high boiling syrup, or "bob syrup", is relativelyviscous and possesses a higher density, and frequently contains asubstantial amount of sugar. Conventionally, the final nougatcomposition is prepared by the addition of the "bob syrup" to the frappeunder agitation, to form the basic nougat mixture. Further ingredientssuch as flavorings, oils, additional sugar and the like may be addedthereafter also under agitation. A general discussion of the compositionand preparation of nougat confections may be found in B. W. Minifie,CHOCOLATE, COCOA AND CONFECTIONERY: Science and Technology, 2nd edition,AVI publishing Co., Inc., Westport, Conn., (1980), at Pages 424-425.

Pharmaceutical tablets of this invention may also be in the form ofchewable forms. This form is particularly advantageous because ofconvenience and patient acceptance and rapid onset of bioactivity. Toachieve acceptable stability and quality as well as good taste and mouthfeel several considerations are important, namely amount of activesubstance per tablet, flavor, compressibility and organolepticproperties of the drug.

The preparation of chewable medicated candy is prepared by proceduressimilar to those used to make soft confectionary. This proceduregenerally involves the formation of a boiled sugar-corn syrup blend towhich is added a frappe mixture. The boiled sugarcorn syrup blend may beprepared from sugar and corn syrup blended in parts by weight ratio of90 to 10: 10 to 90. This blend is heated to temperatures above 250° F.to remove water and to form a molten mass. The frappe is generallyprepared from gelatin, egg albumen, milk proteins such as casein, andvegetable proteins such as soy protein, and the like which are added toa gelatin solution and rapidly mixed at ambient temperature to form anaerated sponge like mass. The frappe is then added to the molten candybase and mixed until homogenous at temperatures between 150° F. and 250°F. The medicament adsorbate can then be added as the temperature of themix is lowered to around 150° F. to 200° F. whereupon additionalingredients are added such as flavors, and colorants. The formulation isfurther cooled and formed to pieces of desired dimensions.

A general discussion of the lozenge and chewable tablet forms ofconfectionery may be found in H. A. Lieberman and L. Lachman,Pharmaceutical Dosage Forms: Tablets Volume 1, Marcel Dekker, Inc., NewYork, N.Y. at pages 289 to 466.

With regard to the chewing gum formulation in particular, the amount ofgum base employed will vary greatly depending on various factors such asthe type of base used, consistency desired and other components used tomake the final product. In general, amounts of about 5% to about 45% byweight of the final chewing gum composition are acceptable for use inchewing gum compositions with preferred amounts of about 15% to about25% by weight. The gum base may be any water-insoluble gum base wellknown in the art. Illustrative examples of suitable polymers in gumbases include both natural and synthetic elastomers and rubbers. Forexample, those polymers which are suitable in gum bases, include,without limitation, substances of vegetable origin such as chicle,jelutong, gutta percha and crown gum. Synthetic elastomers such asbutadiene-styrene copolymers, isobutylene-isoprene copolymers,polyethylene, polyisobutylene and polyvinylacetate and mixtures thereof,are particularly useful.

The gum base composition may contain elastomer solvents to aid insoftening the rubber component. Such elastomer solvents may comprisemethyl, glycerol or pentaerythritol esters of rosins or modified rosins,such as hydrogenated, dimerized or polymerized rosins or mixturesthereof. Examples of elastomer solvents suitable for use herein includethe pentaerythritol ester of partially hydrogenated wood rosin,pentaerythritol ester of wood rosin, glycerol ester of wood rosin,glycerol ester of partially dimerized rosin, glycerol ester ofpolymerized rosin, glycerol ester of tall oil rosin, glycerol ester ofwood rosin and partially hydrogenated wood rosin and partiallyhydrogenated methyl ester of rosin, such as polymers of α-pinene orβ-pinene; terpene resins including polyterpene and mixtures thereof. Thesolvent may be employed in an amount ranging from about 10% to about 75%and preferable about 45% to about 70% by weight to the gum base.

A variety of traditional ingredients such as plasticizers or softenerssuch as lanolin, stearic acid, sodium stearate, potassium stearate,glyceryl triacetate, glycerine and the like for example, natural waxes,petroleum waxes, such as polyurethene waxes, paraffin waxes andmicrocrystalline waxes may also be incorporated into the gum base toobtain a variety of desirble textures and consistency properties. Theseindividual additional materials are generally employed in amounts of upto about 30% by weight and preferably in amounts of from about 3% toabout 20% by weight of the final gum base composition.

The chewing gum composition may additionally include the conventionaladditives of flavoring agents, coloring agents such as titanium dioxide;emulsifiers such as lecithin and glyceryl monostearate; and additionalfillers such as aluminum hydroxide, alumina, aluminum silicates, calciumcarbonate, and talc and combinations thereof. These fillers may also beused in the gum base in various amounts. Preferably the amount offillers when used will vary from about 4% to about 30% by weight of thefinal chewing gum.

In the instance where auxiliary sweeteners are utilized, the presentinvention contemplates the inclusion of those sweeteners well known inthe art, including both natural and artificial sweeteners. Thus,additional sweeteners may be chosen from the following non-limitinglist:

A. Water-soluble sweetening agents such as monosaccharides,disaccharides and polysaccharides such as xylose, ribose, glucose,mannose, galactose, fructose, dextrose, sucrose, sugar, maltose,partially hydrolyzed starch, or corn syrup solids and sugar alcoholssuch as sorbitol, xylitol, mannitol and mixtures thereof.

B. Water-soluble artificial sweeteners such as the soluble saccharinsalts, i.e., sodium, or calcium saccharin salts, cyclamate salts,acesulfam-K and the like, and the free acid form of saccharin.

C. Dipeptide based sweeteners such as L-aspartylphenylalanine methylester and materials described in U.S. Pat. No. 3,492,131 and the like.

In general, the amount of sweetener will vary with the desired amount ofsweeteners selected for a particular chewing gum. This amount willnormally be 0.001% to about 90% by weight when using an easilyextractable sweetener. The water-soluble sweeteners described incategory A above, are preferably used in amounts of about 25% to about75% by weight, and most preferably from about 50% to about 65% by weightof the final chewing gum composition. In contrast, the artificialsweeteners described in categories B and C are used in amounts of about0.005% to about 5.0% and most preferably about 0.05 to about 2.5% byweight of the final chewing gum composition. These amounts areordinarily necessary to achieve a desired level of sweetness independentfrom the flavor level achieved from flavor oils. While water may beadded independently with dry sweeteners, it will generally be added aspart of a corn syrup or corn syrup mixture.

Suitable flavorings include both natural and artificial flavors, andmints such as peppermint, menthol, artificial vanilla, cinnamon, variousfruit flavors, both individual and mixed, and the like are contemplated.The flavorings are generally utilized in amounts that will varydepending upon the individual flavor, and may, for example, range inamounts of about 0.5% to about 3% by weight of the final compositionweight.

The colorants useful in the present invention, include the pigments suchas titanium dioxide, that may be incorporated in amounts of up to about1% by weight, and preferably up to about 0.6% by weight. Also, thecolorants may include other dies suitable for food, drug and cosmeticapplications, and known as F.D. & C. dyes and the like. The materialsacceptable for the foregoing spectrum of use are preferablywater-soluble. Illustrative examples include indigoid die, known as F.D.& C. Blue No. 2, which is the disodium salt of 5,5'-indigotindisulfonicacid. Similarly, the dye known as F.D. & C. Green No. 1, comprises atriphenylmethane dye and is the monosodium salt of4-[4-Nethyl-p-sulfobenzylamino)diphenylmethylene]-[1-(N-ethyl-N-p-sulfoniumbenzyl)-2,5-cyclohexadienimine]. A full recitation of all F.D. & C. and D. & C.and their corresponding chemical structures may be found in theKirk-Othmer Encyclopedia of Chemical Technology, in volume 5, at Pages857-884, which text is accordingly incorporated herein by reference.

Suitable oils and fats that are useable would include partiallyhydrogenated vegetable or animal fats, such as coconut oil, palm kerneloil, beef tallow, lard, and the like. These ingredients are generallyutilized in amounts with respect to the comestible product of up toabout 7.0% by weight, and preferably up to about 3.5% by weight of thefinal product.

It is generally accepted that as the required amount of active substanceper structure gets smaller and/or less bad tasting, the task at arrivingat an acceptable formulation becomes easier due to the greater number offormulations available. Alternately, extremely bad-tasting and/orhigh-dose drugs are difficult to formulate into medicament/chewabletablets. The medicament adsorbates of this invention overcome thesedifficulties.

The quantity of adsorbate used may vary widely depending upon theparticular medicament drug dosage. Amounts of medicament of about 1.0 toabout 400 mg per medicated dosage are useable dependant upon theparticular medicament. Naturally amounts of medicament adsorbate usedwill be higher depending on the therapeutic dosage required and amountof medicament adsorbed on the substrate. Illustrative examples aredescribed below.

The usual dosage of dimenhydrinate is between 50 and 100 mg per tablet.Incorporation of the adsorbate into, for example, a candy base is notdifficult because of its melting point and solvent solubility. It iscompatible with most flavors and is stable over a wide pH range. Thedimenhydrinate when added as the medicament adsorbate avoids its bittertaste and flavoring difficulty.

The medicament adsorbate is generally present with the pharmaceuticallyacceptable carrier in an amount of from about 1% to about 60% by weightof the final composition. The exact amount will be dependent upon theparticular medicament and dosage required.

The present invention is further illustrated by the following examples.All parts and percentages in the examples and throughout thespecification and claims are by weight unless otherwise indicated.

EXAMPLE 1 (Inventive Runs 1 and 2)

This Example demonstrates a method for preparing a dextromethorphanhydrobromide adsorbate.

To 30 grams water is mixed 6 grams dextromethorphan hydrobromide, at awater temperature around 90° C., until the drug was in solution. Thesolution was added to 60 grams magnesium trisilicate having a meanspecific surface area of 506.1 m2/g and mixed until a homogenousdispersion resulted, approximately 30 minutes. The mix was then ovendried at 70° C. until a moisture content of below 15% was obtained. Theproduct was then milled to prepare a white free-flowing powdercontaining 10% by weight dextromethorphan hydrobromide.

An organoleptic evaluation test was performed on the product todetermine the presence or absence of bitterness. The instant product didnot exhibit any bitterness or off taste when tested by a human panel ofexperts.

The specific mean surface area of the materials were measured using theQuantasorb Sorption System (Quantachrome Corporation, N.Y.)

The results are set forth in Table I.

FIG. 1 represents a photomicrograph of magnesium trisilicate of thisinvention magnified 5000×. The Figure depicted shows a flake-likestructure having extensive interstitial spaces. The flake-like characteris evident throughout the entire structure and does not merely appear onthe surface. No agglomeration or other spherical particles are noted.

FIG. 2 represents a photomicrograph of the dextromethorphan HBradsorbate prepared in this inventive example magnified 5000×X. TheFigure depicts a flake-like structure having extensive interstitialspaces. The flake-like character is evident throughout the structure anddoes not merely appear on the surface. No agglomerates or otherspherical particles are noted.

EXAMPLE 2 (Comparative Runs A and B)

This Example demonstrates a dextromethorphan hydrobromide adsorbatebelieved to be prepared by the process of Example 1 of U.S. Pat. No.3,085,942 to Hoffman-La Roche lnc. These materials are at least 10 yearsold. The process used broadly involved forming a mixture ofdextromethorphan hydrobromide and magnesium trisilicate having anaverage particle size of 5-microns by dissolving the dextromethorphanhydrobromide in distilled water (80° C.), and then pouring the resultingsolution onto the magnesium trisilicate. The resulting mixture is thenthoroughly mixed by stirring to form a slurry. The solvent is thenremoved by spray-drying. A white free-flowing powder is obtained.

An organoleptic evaluation test was performed on the adsorbate productto determine the presence or absence of bitterness. The productdemonstrated acceptable characteristics in that it reduced thebitterness of the drug.

The mean specific surface area was measured as in Example 1, Run 1 withresults set forth in Table I.

FIG. 3 represents a photomicrograph of the old magnesium trisilicatemagnified 5000×. The Figure depicts an agglomerated product, with someinterstitial spaces but absence of flake-like character throughout itsstructure.

FIG. 4 represents a photomicrograph of the old dextromethorphan HBradsorbate magnified 5000×. The Figure depicts a smooth surfaced particlelacking interstitial spaces and flaked structure.

                  TABLE I                                                         ______________________________________                                                                Mean                                                                          Specific                                                                      Surface                                                                       Area                                                  Run       Material      (M2/g)   Structure                                    ______________________________________                                        Inventive 1                                                                             Magnesium     506.1    Flaked                                                 trisilicate            (FIG. 1)                                     Comparative A                                                                           Old magnesium 415.1    Agglomerated                                           trisilicate            (FIG. 3)                                     Inventive 2                                                                             Dextromethorphan                                                                            209.8    Flaked                                                 HBr-10%                (FIG. 2)                                               adsorbate                                                           Comparative B                                                                           Old dextrometh-                                                                             66.35    Smooth                                                 orphan HBr-10%         (FIG. 4)                                               adsorbate                                                           ______________________________________                                    

EXAMPLE 3 Inventive Runs 3, 4, 5 and 6 Comparative Runs C, D, E and F

This Example compares the properties derived from variousdextromethorphan HBr adsorbates prepared by the process of Example 1using different magnesium trisilicates from different commercialsources.

The results are set forth in Table II.

                  TABLE II                                                        ______________________________________                                        Magnesium Trisilicate                                                                              Mean                                                                          Specific                                                                      Surface                                                             Adsorbate Area                                                     Run        Taste     (m.sup.2 /g)                                                                             Structure                                     ______________________________________                                        Inventive 3                                                                              Good      441.8      Flaked                                        Inventive 4                                                                              Good      460.4      Flaked                                        Inventive 5                                                                              Good      564.2      Flaked                                        Inventive 6                                                                              Good      --         Flaked                                        Comparative C                                                                            Bitter    181.8      Smooth Surface                                Comparative D                                                                            Bitter    240.8      Smooth Surface                                Comparative E                                                                            Bitter    --         --                                            Comparative F                                                                            Bitter    --         --                                            ______________________________________                                    

EXAMPLE 4 (Inventive Run 7)

This Example demonstrates a method for preparing a dimenhydrinateadsorbate.

To 3,000 grams water is mixed 900 grams dimenhydrinate, at a watertemperature around 90° C., until the drug was in solution. The solutionwas added to 4,000 grams magnesium trisilicate having a mean specificsurface area of at least 400 m² /g and mixed until a homogeneousdispersion resulted, approximately 30 minutes. The mix was then ovendried at 75° C. until a moisture content of below 15% was obtained. Theproduct was then milled to prepare a white free-flowing powdercontaining 22.5% by weight dimenhydrinate.

An organoleptic evaluation test was performed on the product todetermine the presence or absence of bitterness. The instant product didnot exhibit objectional bitterness or off taste when tested by a humanpanel of experts.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention and all suchmodifications are intended to be included within the scope of thefollowing claims.

What is claimed is:
 1. A medicament adsorbate which comprises magnesiumtrisilicate having a surface area of at least 400 m² /g and having aflake-like structure with multiple interstitial spaces, and containingadsorbed therein from about 1% to about 20% by weight of the adsorbateof a medicament drug wherein the medicament drug is selected from thegroup of antinauseants consisting of dimenhydrinate, meclizine andmixtures thereof.
 2. The adsorbate of claim 1 wherein the medicamentdrug is present in the amount of about 5% to about 15% by weight of theadsorbate.
 3. The adsorbate of claim 1 wherein the medicamenttrisilicate has a surface area of about 440 m² /g to about 600 m/g.
 4. Aprocess for preparing a medicament adsorbate which comprises dissolvinga medicament drug in solvent, admixing magnesium trisilicate having asurface area of at least 400 m² /g and having a flake-like structurewith multiple interstitial spaces therewith to prepare a mass having ahomogenous consistency to enable migration of the medicament drug withinthe interstitial spaces of the magnesium trisilicate and recovering themedicament adsorbate product.
 5. A process for preparing a medicamentadsorbate which comprises dissolving a medicament drug wherein themedicament drug is selected from the group of antinauseants consistingof dimenhydrinate, meclizine and mixtures thereof in solvent, admixingmagnesium trisilicate having a surface area of at least 400 m² /g andhaving a flake-like structure with multiple interstitial spacestherewith to prepare a mass having a homogenous consistency to enablemigration of the medicament drug within the interstitial spaces of themagnesium trisilicate and recovering the medicament adsorbate product.6. The process of claim 4 which comprises employing about 30% to about60% solvent by weight of the total composition to prepare a slurry andthereafter removing the solvent from the slurry to form a paste.
 7. Theprocess of claim 6 wherein the paste is dried and recovered as a freeflowing powder.